化疗药物的肾毒性

癌症的化疗仍是一种不完美的疗法,有许多并发症,肾脏更易受化疗药的毒性损害。一、阿霉素:是一种抗生素,用于治疗淋巴瘤等。除了它对心脏的毒性反应外,随心排量减少出现肾前性氮质血症,用药后1～6个月(通常在2个月内)发生。BuN成比例地增加比肌酐为高,盐的滞留使浮肿加重。药物最好每周给予20mg/m~2。二、白细胞介素-2和激活杀伤细胞的淋巴因子:白细胞介素-2刺激T辅助细胞和天然杀伤细胞对肿     

自杀基因联合化疗药物治疗结肠癌的体外研究

目的 研究胞嘧啶脱氨酶基因（CD）联合化疗药物对结肠癌的治疗作用。方法 以重组腺病毒AdCMVCD为载体转移CD基因，在体外研究病毒感染对顺铂（CDDP）、丝裂霉素（MMC）敏感性的影响，化疗药物对AdCMVCD/５-FC直接杀伤作用及“旁观者效应”的影响。结果 病毒感染并不影响Lovo细胞对CDDP、MMC的敏感性；低剂量CDDP、MMC即可明显增强AdDMVCD/5-FC系统的直接杀瘤作用，５-FC的IC50明显降低（P＜0．05），并且增强AdCMVCD/5-FC系统的“旁观者效应”。结论 化疗药物可以增强自杀基因系统对结肠癌的治疗作用，自杀基因和化疗药物有望联合应用于结肠癌的治疗。     

区域化疗对结肠癌肝转移的治疗

目的 探讨不同化疗方法对结肠癌并肝转移及局部复发的影响. 方法 Duke D期结肠癌患者50例,术后分成4组,以肝转移灶切除+区域化疗(n=18)、肝转移灶切除+全身化疗(n=20)、肝转移灶未切除+全身化疗(n=10)及肝转移灶切除术+口服化疗药(n=2)4种方法进行治疗. 结果 18例区域化疗患者随访8年,仍有5名患者存活,1年生存率为94%,3年生存率为55%,5年生存率为27.8%.区域化疗组对治疗结肠癌并肝转移致死亡率明显低于全身化疗及口服化疗药组. 结论 结肠癌术中、术后以FMC方案定期区域化疗,对减少原发灶和肝转移的复发同时提高生存率将起到积极作用.     

逆行隔离灌注化疗可减轻对大鼠肝脏的毒性及药物的泄漏

Objective The retrograde isolated hepatic perfusion (RIHP) model was used to compare with the isolated hepatic perfusion (IHP) model in reducing the rate of normal hepatic tissue toxicity and peripheral drug leakage during chemotherapy in rat liver. Methods A total of 90 male Sprague-Dawley rats weighing 300-350 g were randomized into 3 groups with 30 rats in each. Group A: perfusion with Lactated Ringer'S Solution through arteria hepatica (RA) and portal vein (PV),the inferior vena cava was used as an outflow tract of perfusate. Group B: For isolated hepatic perfusion (IHP), Fluorouracil (5-FU) was added into the perfusate at a dose of 350mg/kg and introduced in to the liver through arteria hepatica, portal vein was perfused by Lactated Ringer'S Solution, and the inferior vena cava was used as an outflow tract of perfusate. Group C: by using retrograde isolated hepatic perfusion (RIHP), the solution which contains 350 mg/kg Fluorouracil (5-FU) was also introduced through arteria hepatica, the inferior vena cava was introduced with Lactated Ringer'S Solution;the portal vein was used as an outflow tract of the perfusate. On day 1, 3, 5 and 7 after the perfusion in all groups, blood serum ALT test and liver histopathology test were performed. The peripheral blood drug levels were measured with high performance liquid chromatographic(HPLC) system in group B and group C. Results The survival rate was 90%, 86.7% and 90% in group A, B and C,respectively. No statistically significant difference was observed in the survival rate among the 3groups. In all the three groups, serum ALT levels were the highest on the first day after IHP: (481.6±207.6)μmol/LingroupA;(1641. 6±658.0) μmol/LingroupBand( 913. 0±353. 5)μmol/Lin group C. Significant higher serum ALT levels were observed by comparing group B and C with A(P＜0. 05). Meanwhile, the serum ALT levels were significantly higher in group B than in group C (P＜0.05). The peaks of peripheral blood drug concentration during the perfusion were 131.2±29.4μg/ml in group B and 65.3±28. 4μg/ml in group C. Significant difference was observed (P＜0. 05). Liver biopsies of group A showed mild changes on the first day after IHP and returned to normal after 7 days. Group B showed severe changes on the first day after IHP and local necrosis still existed after 7 days. Group C showed moderate changes as compared with group B on the first day after IHP and also returned to normal after 7 days. Conclusion Retrograde isolated hepatic perfusion (RIHP) can reduce the liver toxicity compared to isolated hepatic perfusion (IHP). Hopefully, RIHP will be considered as a safer way in regional chemotherapy in liver cancer.     

逆行隔离灌注化疗可减轻对大鼠肝脏的毒性及药物的泄漏

Objective The retrograde isolated hepatic perfusion (RIHP) model was used to compare with the isolated hepatic perfusion (IHP) model in reducing the rate of normal hepatic tissue toxicity and peripheral drug leakage during chemotherapy in rat liver. Methods A total of 90 male Sprague-Dawley rats weighing 300-350 g were randomized into 3 groups with 30 rats in each. Group A: perfusion with Lactated Ringer'S Solution through arteria hepatica (RA) and portal vein (PV),the inferior vena cava was used as an outflow tract of perfusate. Group B: For isolated hepatic perfusion (IHP), Fluorouracil (5-FU) was added into the perfusate at a dose of 350mg/kg and introduced in to the liver through arteria hepatica, portal vein was perfused by Lactated Ringer'S Solution, and the inferior vena cava was used as an outflow tract of perfusate. Group C: by using retrograde isolated hepatic perfusion (RIHP), the solution which contains 350 mg/kg Fluorouracil (5-FU) was also introduced through arteria hepatica, the inferior vena cava was introduced with Lactated Ringer'S Solution;the portal vein was used as an outflow tract of the perfusate. On day 1, 3, 5 and 7 after the perfusion in all groups, blood serum ALT test and liver histopathology test were performed. The peripheral blood drug levels were measured with high performance liquid chromatographic(HPLC) system in group B and group C. Results The survival rate was 90%, 86.7% and 90% in group A, B and C,respectively. No statistically significant difference was observed in the survival rate among the 3groups. In all the three groups, serum ALT levels were the highest on the first day after IHP: (481.6±207.6)μmol/LingroupA;(1641. 6±658.0) μmol/LingroupBand( 913. 0±353. 5)μmol/Lin group C. Significant higher serum ALT levels were observed by comparing group B and C with A(P＜0. 05). Meanwhile, the serum ALT levels were significantly higher in group B than in group C (P＜0.05). The peaks of peripheral blood drug concentration during the perfusion were 131.2±29.4μg/ml in group B and 65.3±28. 4μg/ml in group C. Significant difference was observed (P＜0. 05). Liver biopsies of group A showed mild changes on the first day after IHP and returned to normal after 7 days. Group B showed severe changes on the first day after IHP and local necrosis still existed after 7 days. Group C showed moderate changes as compared with group B on the first day after IHP and also returned to normal after 7 days. Conclusion Retrograde isolated hepatic perfusion (RIHP) can reduce the liver toxicity compared to isolated hepatic perfusion (IHP). Hopefully, RIHP will be considered as a safer way in regional chemotherapy in liver cancer.     

逆行隔离灌注化疗可减轻对大鼠肝脏的毒性及药物的泄漏

目的 采用大鼠肝脏隔离灌注模型探讨逆行隔离灌注(RIHP)较顺行隔离灌注(IHP)能否减少正常肝组织损伤及化疗药物外周泄漏率.方法 将90只体重300～350 g雄性SD大鼠随机分为A、B、C三组,每组30只:A组为空白对照组,经肝动脉及门静脉灌注乳酸林格液,以下腔静脉为灌注液流出道;B组行IHP,经肝动脉灌注含有350 mg/kg的氟尿嘧啶(5-Fu),门静脉灌注乳酸林格液,以下腔静脉为灌注液流出道;C组行RIHP,经肝动脉灌注含有350 mg/kg的氟尿嘧啶(5-Fu),经下腔静脉灌注乳酸林格液,以门静脉为灌注液流出道.术后1、3、5、7 d分别行血清ALT测定及肝组织病理学检查;高效液相色谱分析仪检测B、C组术中外周血药浓度.结果 三组术后3 d存活率分别为90.0%、86.7%和90.0%,三者差异无统计学意义.三组血清ALT均在术后第一天达到峰值,A组为(481.6±207.6)μmol/L;B组为(1641.6±658.0)μmol/L;C组为(913.0±353.5)μmol/L.B、C组均显著高于A组(P＜0.05);B组显著高于C组(P＜0.05).B组与C组术中外周血药浓度峰值分别为(131.2±29.4)μg/ml和(65.3±28.4)μg/ml.两组外周浓度有显著性差异(P＜0.05).A组术后肝脏病理改变较轻,术后7 d基本恢复正常;B组术后肝脏病理学改变相对严重,术后7 d局部仍可见坏死灶;C组术后肝脏病理改变后较A组严重,但较B组轻,术后7 d基本恢复正常.结论 RIHP较之IHP能够显著减轻化疗药物对正常肝组织的毒副作用和药物的外周泄漏,有望成为一种对肝癌更加有效安全的区域化疗方法.     

结肠癌术后辅助化疗

<正>结肠癌是临床最常见的恶性肿瘤之一。在美国,结肠癌发病率占所有癌症的第4位,而病死率为第2位。2011年美国约有101340例结肠癌和39870例直肠癌的新发病例;而同年估计将有49380例患者死于结肠癌[1]。我国近年来结肠癌在普通人群中的发病率也有逐渐增高的趋势,达到年均4%[2]。对结肠癌患者最主要的干预措施为手术切除肿瘤,即肿瘤学原则切除所有病变组织和清扫局部淋     

前药热化疗对裸鼠结肠癌肝转移的作用

目的 观察胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝转移的作用.方法 45只裸鼠随机分为3组,分别给予不同的治疗方法,观察各组肝转移率、肝转移瘤数目、病理学变化、肿瘤细胞凋亡指数,检测肿瘤组织中CD基因的表达情况.结果 对照组、5-FC治疗组、5-FC热疗组平均肝脏转移瘤数和肝脏转移率分别为4.6000±1.2649、2.2000±0.9189、0.5000±0.8498;100%、40%、20%;肿瘤细胞凋亡指数平均为4.59%、9.87%和17.40%,5-FC热疗组可见较多的凋亡小体形成.结论 CD/5-FC系统热化疗对裸鼠转CD基因LoVo细胞结肠癌肝转移有明显的抑制作用.     

结肠癌腹腔内淋巴化疗的临床研究

目的　观察结肠癌患者术前麻醉诱导期联合应用善宁、卡铂对结肠淋巴结铂浓度的影响 ,以及预防性腹腔内淋巴化疗对术后腹膜后淋巴结转移的影响。　方法　 182例结肠癌患者随机分为预防性腹腔内淋巴化疗组 (90例 )和对照组 (92例 ) ,均行根治性切除术。淋巴化疗组患者 ,在术前麻醉诱导期开始联合应用善宁 (0 1mg ,2次 )、卡铂 (2 0 0mg) ;对照组仅用卡铂 (2 0 0mg)腹腔内化疗 ,比较 2组患者术中结肠边缘淋巴结、中间淋巴结以及中央淋巴结铂浓度。 2组患者术后继续腹腔内淋巴化疗或腹腔内化疗 ,以腹部CT检查比较其对术后腹膜后淋巴结转移的影响。　结果　腹腔内淋巴化疗组患者用药 2、3h后 ,边缘淋巴结、中间淋巴结以及中央淋巴结铂浓度明显高于对照组 ;术后腹膜后淋巴结转移率明显低于对照组 ,差异均有极显著性意义 (P <0 0 1)。 2组门静脉血液铂浓度、转移淋巴结与未转移淋巴结之间铂浓度差异均无显著性意义 (P >0 0 5 )。　结论　联合应用善宁、卡铂可明显提高结肠淋巴结铂浓度 ,减少术后淋巴转移 ,是一种有效的腹腔内淋巴化疗方式。     

结肠癌辅助性化疗开始时间延迟的原因

<正>辅助化疗会提高结肠癌患者生存率,但两个荟萃分析证明,辅助化疗时间的延长会降低生存率,由此作者研究了辅助化疗时间延长的主要影响因素。580例在东安大略省两家癌症研究所于2005年8月至2010年11月期间患有结肠癌且接受辅助化疗的患者接受研究。采集了患者姓名、疾病及治疗特点(包括手术至辅助化疗的间隔时间)信息。患者被分成3组:因术后     

癌症化疗毒性与麻醉

随着肿瘤治疗学的发展,癌症病人手术前大多已接受放射治疗、免疫治疗和(或)化学治疗,病人全身面临化疗药物的代谢毒性和细胞破坏,器官结构和功能可能已蒙受变性损害。针对这类特殊情况,麻醉医师必须警惕化疗与麻醉之间的相互不良影响,麻醉的重点在尽量避免加重器官的再损害。麻醉前除明确病人患何种肿瘤、其性质与进展、是否已接受化疗或放疗外,应特别重视辩识化疗或放疗是否已经引起生命器官(肺、心脏、CNS、血液、肝脏、肾脏、血管及代谢)毒性改变。下文列述癌症化疗过程中最常见的严重毒性作用。     

电穿孔化疗对结肠癌裸鼠移植瘤模型的作用研究

目的:观察电穿孔技术结合博莱霉素化疗对结肠癌裸鼠移植瘤的抗肿瘤效果,为本疗法的临床应用提供实验依据。方法:于裸鼠左前肢皮下接种人结肠癌LoVo单细胞悬液,3周后成功建立结肠癌裸鼠皮下移植瘤模型40只,随机将其分为电穿孔化疗(B E )组、单纯化疗(B E-)组、单纯电穿孔(B-E )组和阴性对照(B-E-)组,每组10只。动态观察肿瘤大小,治疗第7天处死小鼠并取出皮下肿瘤称重,。并观察其组织学改变。结果:B E 组裸鼠移植瘤体积较其他各组明显缩小(P<0.01),该组1只裸鼠的移植瘤呈完全缓解,部分缓解7只;B-E 和B E-组内各有1只部分缓解,而B-E-组中无一有效。B E 组有效率与其余各组的差别有统计学意义(P<0.01)。组织学观察也显示B E 组的移植瘤内大片肿瘤细胞坏死、血管损伤和炎细胞浸润。结论:电穿孔化疗可显著增强结肠癌裸鼠皮下移植瘤对化疗的敏感性,疗效明显,有可能成为结直肠癌治疗的一种新方法。     

热化疗对结肠癌LOVO细胞胞嘧啶脱氨酶基因表达的影响

目的 探讨温热疗法对转染胞嘧啶脱氨酶基因的基因表达的影响.方法 脂质体法将质粒G1CEACDNa转染结肠癌LOVO细胞,G418筛选抗体克隆并扩增,给予前药5-氟胞嘧啶(5-FC)进行热化疗;以β-actin为内参照用实时荧光定量PCR检测热化疗前后CD基因表达量的变化.结果 实时荧光定量PCR(Real-Time RT-PCR)检测得到热化疗前CD基因表达的CT值29.5300±1.1974,B.actinct值20.8200±2.7385;热化疗后CD基因表达的CT值30.285±1.201,β-actinet值21.225±2.237;行ΔΔCt法进行相对定量比较差异无统计学意义(P＞0.05,t=1.4521,v=38).结论 温热疗法对转染G1CEACDNa的LOVO细胞CD基因的表达无明显影响.     

原发性肝癌对化疗药物敏感性的研究

目的 研究化疗药物对原发性肝癌细胞的敏感性。方法 应用ＭＴＴ法及流式细胞仪,选择１７种化疗药物对２０例经手术切除的原发性肝癌标本进行化疗药物２性的检测。结果 对原发性肝癌细胞平均抑制率大于５０％的化疗药物为异环磷酰胺、氟脲嘧啶、ＶＭ－２６（威猛）、ＴＡＡ（泰素）、环磷酰胺及ＤＤＰ（顺铂）。结论 根据联合化疗的原则,对于原发性肝癌患者选用的化疗方案为：以氟脲嘧啶为主、配合顺铂等其他一种或二种敏感的化     

化疗药物对胃癌细胞的杀伤效应

目的 探讨化疗药物对胃癌细胞的杀伤效应.方法 收集2006年4月至2007年2月济南军区总医院手术切除的84例胃癌标本,新鲜胃癌组织制备单细胞悬液,分别加入羟基喜树碱、顺铂、阿霉素、5-氟尿嘧啶和丝裂霉素培养48 h.MTT法观察药物作用后癌细胞活性变化.免疫组织化学检测生存素及PTEN的表达.采用χ~2、秩和检验和Fisher确切概率法分析数据.结果 不同化疗药物对胃癌细胞杀伤效应不同,分化差的胃癌较分化好的胃癌对化疗药物敏感.在印戒细胞癌、黏液腺癌及低分化腺癌中生存素阳性率高于乳头状腺癌及管状腺癌,差异有统计学意义(χ~2=10.625,P<0.05);而FFEN表达与生存素相反,差异有统计学意义(χ~2=6.060,P<0.05).生存素与5-氟尿嘧啶及阿霉素的体外耐药有关(χ~2=6.609,6.350,P<0.05).结论 MTT体外药敏实验有助于筛选个体有效化疗药物.生存素参与了肿瘤细胞化疗耐受,生存素与PTEN的表达有关.     

胰腺癌细胞对化疗药物敏感性的测定

目的 探讨人胰腺癌细胞株对常用化疗药物及其相互配伍的敏感性，为临床合理用药提供理论依据。方法 将人胰腺癌细胞株（Ｐ３、ＳＷ１９９０、Ｃａｐａｎ－２）细胞接种于９６孔培养板，分别加入不同配伍及不同浓度的化疗药物，作用一定时间后采用噻唑蓝法（ＭＴＴ法）测定其抗癌敏感性。结果 以５－氟脲嘧啶和丝裂霉素为基本的三联用药在抑制率相当的情况下，其组成中各药物剂量仅为单一用药剂量的１／５０；联合用药方案中以５－